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Adjunctive systemic therapy: A reasonable option for patients with muscle-invasive bladder cancer
It is with considerable trepidation that I undertake the assignment to comment on — nay, adjudicate — the “point” and “counter” positions staked out by two of my favorite people: Ian F. Tannock, MD, PhD, and Derek Raghavan, MD, PhD.
One of the advantages of long experience is the opportunity to nurture relationships — and disagreements — among those who are similarly experienced in my chosen discipline: genitourinary medical oncology.
I think Tannock and Raghavan would agree, the number of careers to be counted are limited among the ranks of genitourinary medical oncologists with experience similar to those that we have.
Not to imply that experience and longevity have anything to do with the likelihood of being correct, but one thing experience does ensure is that you have heard similar arguments again and again. This argument is an example of that concept.
The question: “Is adjuvant chemotherapy appropriate to consider for fit individuals who have not received neoadjuvant chemotherapy and have completed definitive local therapy — irradiation or cystectomy or both — for muscle-invading bladder cancer?”
Cutting right to the chase: My answer is a resounding yes!
My reasons for this conclusion are exercises in oncologic logic, rather than level-one evidence. That logic illustrates some of the more perplexing issues in genitourinary oncology.
1. Combination chemotherapy works strikingly well in some patients with widely metastatic bladder cancer and not in others. We have precious little information with which to guess who will respond. A dominant factor seems to be disease burden/visceral metastases. Complete remissions and long-term survival following MVAC (methotrexate, vinblastine, doxorubicin and cisplatin), gemcitabine–cisplatin or accelerated MVAC occur more often than similar responses in metastatic breast, lung, colorectal, kidney or prostate cancers, to name only a few.
2. Neoadjuvant chemotherapy improves survival in muscle-invading bladder cancer.
It is implausible for me to imagine that these two observations do not translate to improved outcomes among patients following cystectomy or definitive irradiation for this disease. However, we should all be ashamed that we do not know the answer to this question, because there is no well-designed, large randomized clinical trial. In their trial, Cognetti and colleagues randomly assigned fewer than 300 patients effectively to three arms. Further, Sternberg and colleagues noted that their own trial is “limited in power.”
I remember naively suggesting around 1985, as the cystectomy with or without MVAC trial was being designed, that we should conduct, in parallel, an adjuvant trial — ah, the naiveté of youth!
Fortunately, more insightful trialists than me prevailed. Little did I recognize that it would take 11 years to accrue 317 patients to answer the neoadjuvant question! Who could have imagined that, 10 years after the publication of this paper, 70% of individuals with muscle-invading bladder cancer would not be offered neoadjuvant chemotherapy in a comprehensive cancer center?
Unfortunately, in genitourinary oncology, we have been slow in asking and applying the answers to questions involving multidisciplinary care.
For example, the National Surgical Adjuvant Breast and Bowel Project reported in 1975 the results of the use of melphalan in early breast cancer. When were the first trials of an effective therapy in advanced disease as combined-modality therapy in genitourinary cancer?
Multimodality therapies have been slow to develop in genitourinary cancer. Given that reality, one must make clinical recommendations based on data at hand. As Sir William Osler,FRS, FRCP — a physician I admire even more than Raghavan and Tannock — has said: “Medicine is a science of uncertainty and an art of probability.”
I read the question as: “What should a physician recommend with respect to adjuvant therapy following completion of local therapy in a patient with muscle-invading bladder cancer?”
My answer: Data and logic make adjunctive systemic therapy (gemcitabine–cisplatin, accelerated MVAC or MVAC) a completely reasonable option to be discussed with a patient and their family.
References:
Abida W, et al. Hematol Oncol Clin North Am. 2015;doi:10.1016/j.hoc.2014.10.005.
Cognetti F, et al. Ann Oncol. 2011;doi:10.1093/annonc/mdr354.
Grossman HB, et al. N Engl J Med. 2003;doi:10.1056/NEJMoa022148.
Rehman S, et al. Urology. 2013;doi:10.1016/j.urology.2013.07.055.
Sternberg CN, et al. Lancet Oncol. 2015;doi:10.1016/S1470-2045(14)71160-X.
von der Maase H, et al. J Clin Oncol. 2005;doi:10.1200/JCO.2005.07.757.
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Donald L. Trump, MD, FACP, is CEO and executive director of Inova Schar Cancer Institute. He also is HemOnc Today’s associate editor for medical oncology. He can be reached at donald.trump@inova.org.
Disclosure: Trump reports no relevant financial disclosures.